OVERVIEW: What every practitioner needs to know

Are you sure your patient has epidermolysis bullosa? What are the typical findings for this disease?

Epidermolysis bullosa (EB) presents with blisters/bullae on the skin in response to minimal trauma. The typical location is on friction-prone areas such as hands, feet, knees, and elbows.

The severity and extent of the blistering depends on the type of EB (see below). The presence of blisters can lead to pain itching and affect daily activities and quality of life.

Classification

There are four major types of EB that result from protein abnormalities affecting the dermoepidermal junction. Lack of production, or production of proteins that are structurally abnormal, leads to fragility of the skin and separation of the skin layers. The clinical presentation, severity, and overall prognosis depends on the level of the split within the dermoepidermal junction.

Epidermolysis bullosa simplex (EBS) results from abnormal production of the proteins that make the desmosomal and hemidesmosomal unit (keratin 5, 14, plectin). Other rare variants of EBS may involve transglutaminase 5, desmoplakin, plakoglobin, plakophilin 1, integrin, exophilin 5, and bullous pemphigoid antigen-1. These mutations lead to blistering above the basement membrane. Most of the forms are autosomal dominantly inherited. Its clinical manifestations are primarily skin related of various severity depending on the EBS subtype. Overall, these patients have a better prognosis than do those with the other forms of EB; long-term survival is unaffected.

Junctional epidermolysis bullosa (JEB), is the result of abnormal proteins (laminin 332, integrin, collagen XVII) that are present at the basement membrane. The most severe subtype, called generalized severe JEB, is characterized by severe skin and mucosal blistering that leads to mortality within the first few years of life. The other forms (generalized intermediate, localized) have milder presentations and are compatible with long-term survival.

Dystrophic epidermolysis bullosa (DEB) is the result of collagen VII mutations that create a split below basement membrane. As the split is lower, the resulting blisters are deeper and heal with scarring. There are two major subtypes, dominant DEB (DDEB) and recessive DEB (RDEB). The recessive forms produce lifetime blistering, significant extracutaneous findings, and decreased survival, particularly in the generalized forms.

Kindler syndrome (KS) is the result of fermitin family homolog 1 (kindlin-1) mutations. It is characterized by blistering at multiple levels within the basement membrane and unique clinical features from other EB types, such as photosensitivity. KS is autosomal recessively inherited. KS produces significant skin findings (blistering is more common in children than in adults) and extracutaneous findings (including oral cavity abnormalities, GI tract abnormalities, pseudosyndactyly). Long-term survival is not commonly affected.

Would imaging studies be helpful? If so, which ones?

Imaging studies are not useful.

Confirming the diagnosis

Rule out other entities with viral and bacterial studies.

Skin biopsy establishes the diagnosis offers some insight into the prognosis, depending on the protein affected (e.g., degree of staining for laminin 332 on immunophenotyping may be predictive of severe, generalized JEB (no staining), or localized variant of JEB [some staining]).

Molecular diagnosis confirms the diagnosis of EB as well as the type and subtype. It can help the clinician with long-term prognosis and can help families with prenatal testing.

If you are able to confirm that the patient has epidermolysis bullosa, what treatment should be initiated?

There is no curative treatment for EB. The goals of management are to prevent blistering, recognize and manage complications and improve quality of life.

Skin Care

Avoidance of sticky tapes and probes directly on the skin (use soft silicone fixation tape to secure devices and use a silicone medical adhesive remover)

Prevention of blistering in the neonatal/infantile period (gentle handling, invert clothing so the seams are on the outside, place monitor probes on silicone dressings instead of on the skin, remove elastic layer of the diaper, use soft silicone nipples for feeding to prevent oral blisters, use "egg crate" mattress or sheepskin on beds)

Management of open blisters (the fluid can lead to further blistering and causes pain; need to drain fluid by opening the blister with a sterile needle leaving the blister roof intact)

Management of skin wounds

Nonstick silicone dressings

Avoid daily dressing changes to minimize trauma

Exudative wounds require two layers of dressings (contact mesh layer and a secondary dressing to absorb exudate; only the top layer is replaced as needed, the contact one can be left in place for up to 1 week) or a foam dressing

Chronic wounds are colonized with bacteria; use antimicrobial agents topically or silver dressings

What are the possible outcomes of epidermolysis bullosa?

Prognosis of EB depends on the type and subtype. Generally, EBS, generalized, intermediate JEB, localized JEB, dominant forms of DEB (DDEB), and KS are associated with a better prognosis than is generalized, severe JEB and generalized, severe or generalized, intermediate recessive DEB (RDEB). Mortality in childhood is related to sepsis, airway compromise, and dilated cardiomyopathy, whereas in adulthood it is due to invasive squamous cell carcinoma. The cumulative mortality by age 15 years is 60% for JEB and 8% for recessive DEB.

What causes this disease and how frequent is it?

Genetics are the cause of this disease. The exact prevalence is unknown.

How do these pathogens/genes/exposures cause the disease?

This is a genetic disorder leading to partial or complete loss of structural proteins that are essential for the integrity of the basement membrane, leading to skin fragility.

What complications might you expect from the disease or treatment of the disease?

Chronic anemia

Failure to thrive

Delayed puberty

Osteoporosis

Dilated cardiomyopathy

Squamous cell carcinoma

Are additional laboratory studies available; even some that are not widely available?

Ongoing controversies regarding etiology, diagnosis, treatment

Because of the rarity of the disease and the wide spectrum of severity, there are no uniform guidelines of care. In addition, most of the recommended "ideal" dressings are not widely available or affordable. New therapies aimed at correction of the genetic defect are being attempted at present.